This application is Part B of a competing renewal to the Pittsburgh component of the Multicenter AIDS Cohort Study (MACS) Cooperative Agreement (1 U01 AI035041), the companion to the Part A composite application that is being submitted by CAMACS. The MACS began in 1983 as a longitudinal study of the natural history of AIDS in men who have sex with men (MSM). This request is for an additional five years of support for clinical follow-up and laboratory testing of the cohort of MSM in the Pittsburgh MACS. The broad objectives of the Pittsburgh MACS are to fulfill the specific aims of the Part A master MACS application, and do special studies locally in Pittsburgh to enhance our epidemiologic and pathogenesis knowledge in relation to treatment intervention, and development of immunotherapeutic and prophylactic vaccines. Our specific aims are to determine the long-term natural and treated history of HIV infection in MSM, characterize the responses to HIV therapy, including psychological and behavioral predictors, examine the effects of HIV and prolonged HIV therapy exposure on lipodystrophy, diabetes, cardiovascular disease, liver disease, malignancies, neurocognitive function, substance use, kidney disease, and other outcomes, assess the effects of aging on the clinical course of HIV and HIV therapy, examine the interaction between host genetics and HIV, define HIV pathogenesis, characterize HIV-associated cancers including identification of risk factors, determine socio-behavioral factors that affect HIV transmission and disease progression, characterize concomitant infections and their effects on HIV disease progression, examine the effects of substance abuse on antiretroviral treatment effectiveness, maintain longitudinally collected epidemiological data and biological specimen repository as a platform to facilitate natural history and pathogenesis studies, perform clinical and lab testing of MSM in the Pittsburgh MACS, including T-cell subsets, anti-HIV Ab, HIV viral load, hepatitis B virus and hepatitis C virus testing, serum lipid/insulin/glucose levels, liver function tests, renal function and cardiovascular studies. This research has direct relevance to the mission of the NIH to cure and prevent HIV infection and AIDS. RELEVANCE: As part of the MACS research consortium, the Pittsburgh MACS proposes to continue its 25 year scientific investigation into the natural history of HIV/AIDS. This research provides insight into the mechanisms of HIV infection, the effects of HIV therapy, and development of therapeutic and preventative vaccines for HIV infection. It is highly relevant to HIV/AIDS public health programs of the NIH.